Hsi Chang

A 7-year-old girl with acute myelogenous leukemia with multilineage dysplasia received unrelated cord blood transplantation but developed hemophagocytic syndrome (HPS) after sepsis with methicillin-resistant coagulase-negative staphylococci before engraftment. Bone marrow aspiration on day 20 revealed a markedly increased number of activated macrophages showing hemophagocytosis. The presence of donor-type chimera in the bone marrow was confirmed at that time. We therefore quickly started immunosuppressive and antibacterial treatment. Although her condition gradually improved, the patient suffered graft failure due to HPS. She received peripheral blood stem cell transplantation from her HLA 2-loci-mismatched mother on day 54 and continued in complete remission 12 months after the second transplantation. The results in this case suggested that because of fetomaternal microchimerism it may be useful to select an HLA-haploidentical mother as a backup donor for stem cell transplantation.

There is an increasing number of reported cases with neurological manifestations of COVID-19 in children. Symptoms include headache, general malaise, ageusia, seizure and alterations in consciousness. The differential diagnosis includes several potentially lethal conditions including encephalopathy, encephalitis, intracranial hemorrhage, thrombosis and adrenal crisis. We report the case of a 17-year-old boy with a positive antigen test of COVID-19 who presented with fever for one day, altered mental status and seizure, subsequently diagnosed with adrenal insufficiency. He had a history of panhypopituitarism secondary to a suprasellar craniopharyngioma treated with surgical resection; he was treated with regular hormone replacement therapy. After prompt administration of intravenous hydrocortisone, his mental status returned to normal within four hours. He recovered without neurologic complications. Adrenal insufficiency can present with neurological manifestations mimicking COVID-19...

Background: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal brain tumor most commonly presenting in young children. Methods: We performed a nationwide, population-based study of AT/RT (ICD-O-3 code: 9508/3) in Taiwan using the Taiwan Cancer Registry Database and the National Death Certificate Database. Results: A total of 47 cases (male/female = 29:18; median age at diagnosis, 23.3 months (IQR: 12.5–87.9)) were diagnosed with AT/RT between 1999 and 2014. AT/RT had higher prevalence in males (61.70%), in children < 36 months (55.32%), and at infratentorial or spinal locations (46.81%). Survival analyses demonstrated that patients ≥ 3 years of age (n = 21 (45%)) had a 5y-OS of 41% (p < 0.0001), treatment with radiotherapy only (n = 5 (11%)) led to a 5y-OS of 60%, treatment with chemotherapy with or without radiotherapy (n = 27 (62%)) was associated with a 5y-OS of 45% (p < 0.0001), and patients with a supratentorial tumor (n = 11 (23%)) had a 5...

Whether febrile seizures (FS) produce long-term injury to the hippocampus or other brain structures is a critical question concerning focal onset seizures in children. Our aims are to evaluate the effect of FS on subfields of the hippocampus, thalamic nuclei, amygdala, cortical thickness, and surface area quantitatively in children with FS who later developed focal seizures and to identify biomarkers based on MRI structures. Children who had focal onset seizures with or without previous FS and normal 3-T MRI findings were included retrospectively. The MRI was performed within 2 years after the onset of focal seizures. Age-matched controls were also recruited. Hippocampal subfields and thalamic nuclei, amygdala volumes, cortical thickness, and cortical surface area in individual cortical regions were segmented by FreeSurfer version 7.1.1. Volumetric and morphometric data among children who had focal seizures with or without previous FS, as well as controls, were compared and correlated with clinical parameters. Children with a history of FS who had focal seizures exhibited smaller right cornu ammonis (CA) 1 and right molecular cell layer of the hippocampus, compared to those without FS. A larger left hippocampal fissure was also found in FS with focal seizures compared to age-matched controls. There were no statistically significant differences in each nucleus of the thalamus, amygdala, cortical thickness, and surface area of each cortical region among the three groups. A smaller whole hippocampal volume was found for the right hippocampus in children with FS and focal seizures compared to those without FS. A trend of negative correlation was found between the frequency of FS and the left and right CA1 subfield volume ratios of the hippocampus. We concluded that multiple episodes of FS may be associated with a trivial difference in volume reduction in the CA1 and molecular layer of the right hippocampus and an enlarged hippocampal fissure of the left hippocampus, but not with individual cortical thicknesses, surface area, thalamic nuclei, or amygdala in children with focal onset seizures.The hippocampal subfield CA1 and molecular layer of the right hippocampus may be more vulnerable than the cortices in children with focal seizures who experienced multiple FS episodes. This study highlights the minimal differences in brain volumes among children with recent onset focal seizures with or without FS history and controls, suggesting that the brain injurious aspects of the FS and recent onset focal seizures may have been previously overstated. This suggests that physicians can be reassuring about brain injury associated with these seizure types when discussing outcomes with parents and patients.

BACKGROUND Epileptic surgery is the potentially curative treatment for children with refractory seizures. The study aimed to quantify and analyze high frequency oscillation (HFO) ripples and interictal epileptiform discharges (EDs) in intraoperative electrocorticography (ECoG) between malformation of cortical dysplasia (MCD) and non-MCD children with MRI-lesional focal epilepsy, and evaluate of seizure outcomes after epileptic surgery. METHODS The intraoperative ECoG was performed before and after lesionectomy. Quantifications of HFO ripples and interictal EDs of ECoG by frequency, amplitude, and foci of intraoperative ECoG were performed based on electrode location, and the characteristics of ECoG recordings were analyzed in each patient based on their histopathology. Seizure outcome after surgery according to their quantitative ECoG findings was analyzed. RESULTS Frequency of EDs and HFO ripple rates in preresection ECoG were significantly higher in children with MCD compared with non-MCD (p = 0.018 and p = 0.002, respectively). Higher frequencies of EDs and ripple rates in preresection ECoG were observed in residual seizures than in seizure-free children (p = 0.045 and p = 0.005, respectively). Clinically, children with residual seizures after surgery were significantly younger at the onset, had a trend of higher seizure frequency and higher spike frequency of presurgical videoEEG. CONCLUSION Our results suggested that quantification of intraoperative ECoG predicted seizure outcomes and reflected different ED pattern and frequencies between MCD and non-dysplastic histopathology among children who underwent resective epileptic surgery. The results of our study were encouraging and indicated that intraoperative ECoG improved the outcomes of surgery in children with epilepsy.

Spinal sarcopenia is a complex and multifactorial disorder associated with a loss of strength, increased frailty, and increased risks of fractures and falls. In addition, spinal sarcopenia has been associated with lumbar spine disorders and osteoporosis, which renders making decisions on treatment modalities difficult. Patients with spinal sarcopenia typically exhibit lower cumulative survival, a higher risk of in-hospital complications, prolonged hospital stays, higher postoperative costs, and higher rates of blood transfusion after thoracolumbar spine surgery. Several studies have focused on the relationships between spinal sarcopenia, appendicular muscle mass, and bone-related problems—such as osteoporotic fractures and low bone mineral density—and malnutrition and vitamin D deficiency. Although several techniques are available for measuring sarcopenia, each of them has its advantages and shortcomings. For treating spinal sarcopenia, nutrition, physical therapy, and medication ha...

Background Convulsive status epilepticus (CSE) prevention is critical for pediatric patients with epilepsy. Immediate intervention before CSE reduce severity. Despite its wide usage as an anticonvulsant, valproic acid (VPA) results in harmful side effects such as dose-dependent hepatotoxicity. Hence, reducing VPA dosage to minimize side effects while maintaining its efficacy is necessary, and transcranial photobiomodulation (tPBM) add-on therapy could facilitate this. We recently demonstrated for the first time that tPBM at a wavelength of 808 nm attenuated CSE in peripubertal rats. However, the effects of VPA with the add-on therapy of tPBM prior to seizures have not yet been explored. This study investigated whether adding tPBM to VPA exerts synergistic effect for CSE prevention in peripubertal rats. Methods A gallium-aluminum-arsenide laser (wavelength of 808 nm with an exposure duration of 100 s and irradiance of 1.333 W/cm2 at the target) was applied transcranially 30 min after...

Sarcomas of bone, soft tissue, or neural origin may occasionally invade the central nervous system (CNS), causing diagnostic and therapeutic challenges. We aim to investigate the clinical features of sarcomas involving the CNS at initial presentation. During 2015/01–2019/12, nine consecutive patients (4 Males and 5 Females) younger than 30 years of age treated at a University Healthcare System in Northern Taiwan were included. The median age was 8.7 years (range, 2–24 years); diagnoses were Ewing Sarcoma with EWSR1 rearrangements (n=4), CIC-NUTM1 Sarcoma (n=1), Osteosarcoma (n=2), Malignant Peripheral Nerve Sheath Tumor (MPNST; n=1), and extramedullary myeloid sarcoma (n=1). The tumors originated from the skull (n=1), dura (n=1), vertebra (n=4), spinal canal (n=1), or extra-CNS sites (n=2). Four patients had metastases (1 Ewing sarcoma, 2 osteosarcoma, and 1 extramedullary myeloid sarcoma). The main symptom at diagnosis was facial/eye pain (n=2), back pain (n=3), arm weakness (n=1),...

Background Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damage but also strengthen the muscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin (mSC) on satellite cells (SCs), which are known as the muscle stem cells. Methods The myogenic cells, included SCs (Pax7+) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridine assessed simultaneously. The molecular signal pathway was further investigated by using Wester...

Recently multipotent stem cells have been established from neonatal mouse testis (Shinohara et al, Cell 2004). This multipotent germline stem cell (mGS) is very similar to embryonic stem cells. It differentiates into various types of somatic cells in vitro and produces teratomas after inoculation into mice. Here we show the characteristics of hematopoietic development from mGS cells. mGS cells were maintained on mitomycin C treated mouse embryonic fibroblasts. In undifferentiated state, surface markers were almost the same among mGS, ES and EG cell; E-cadherin+, β1 integrin+, CD31+ and c-kit+. For induction, undifferentiated mGS cells were cultured on OP9 stromal cell line. Four days after induction, we detected and sorted FLK1+ cells as much as ES cells. Flk1+ cells were further cultured on OP9 with various cytokines. Erythroid, myeloid, lymphoid, megakaryocyte and mast cells as well as endothelial cells and beating cells were obtained in the same manner as the induction of ES cell...

Background Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damage but also strengthen the muscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin (mSC) on satellite cells (SCs), which are known as the muscle stem cells. Methods The myogenic cells, included SCs (Pax7+) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridine assessed simultaneously. The molecular signal pathway was further investigated by using Wester...

Induced pluripotent stem (iPS) cells, which are a type of pluripotent stem cell generated from reprogrammed somatic cells, are expected to have potential for patient-oriented disease investigation, drug screening, toxicity tests, and transplantation therapies. Here, we demonstrated that murine iPS cells have the potential to develop in vitro into skeletal muscle stem/progenitor cells, which are almost equivalent to murine embryonic stem cells. Cells with strong in vitro myogenic potential effectively were enriched by fluorescence-activated cell sorting using the anti-satellite cell antibody SM/C-2.6. Furthermore, on transplantation into mdx mice, SM/C-2.6(+) cells exerted sustained myogenic lineage differentiation in injured muscles, while providing long-lived muscle stem cell support. Our data suggest that iPS cells have the potential to be used in clinical treatment of muscular dystrophies.

Satellite cells are myogenic stem cells responsible for the postnatal regeneration of skeletal muscle. Here we report the successful in vitro induction of Pax7-positive satellite-like cells from mouse embryonic stem (mES) cells. Embryoid bodies were generated from mES cells and cultured on Matrigel-coated dishes with Dulbecco's modified Eagle medium containing fetal bovine serum and horse serum. Pax7-positive satellite-like cells were enriched by fluorescence-activated cell sorting using a novel anti-satellite cell antibody, SM/C-2.6. SM/C-2.6-positive cells efficiently differentiate into skeletal muscle fibers both in vitro and in vivo. Furthermore, the cells demonstrate satellite cell characteristics such as extensive self-renewal capacity in subsequent muscle injury model, long-term engraftment up to 24 wk, and the ability to be secondarily transplanted with remarkably high engraftment efficiency compared to myoblast transplantation. This is the first report of transplantable, functional satellite-like cells derived from mES cells and will provide a foundation for new therapies for degenerative muscle disorders.

Recent studies have indicated that bone marrow cells can regenerate damaged muscles and that they can adopt phenotypes of other cells by cell fusion. Our direct visualization system gave evidence of massive muscle regeneration by green fluorescent protein (GFP)-labeled CD45+c-Kit+Sca-1+Lin- cells (KSL cells), and we investigated the role of KSL cells in muscle regeneration after transplantation with or without lethal irradiation. In the early phase, GFP signals were clearly observed in all the muscles of only irradiated mice. Transverse cryostat sections showed GFP+myosin+ muscle fibers, along with numerous GFP+ hematopoietic cells in damaged muscle. These phenomena were temporary, and GFP signals had dramatically reduced 30 days after transplantation. After 6 months, GFP+ fibers could hardly be detected, but GFP+c-Met+ mononuclear cells were located beneath the basal lamina where satellite cells usually exist in both conditioned mice. Immunostaining of isolated single fibers revealed GFP+PAX7+, GFP+MyoD+, and GFP+Myf5+ satellite-like cells on the fibers. Single-fiber cultures from these mice showed proliferation of GFP+ fibers. These results indicate two different roles of KSL cells: one leading to regeneration of damaged muscles in the early phase and the other to conversion into satellite cells in the late phase.

Case report. The authors present a case of atypical Burkitt's lymphoma with multiple epidural involvements. Spinal cord compression in children is an emergency that requires urgent attention to minimize neurologic dysfunction. Although it is not life-threatening in most patients, cord compression can cause severe neurologic morbidity. Because the patient showed rapid neurologic deterioration, we started chemotherapy and high-dose steroids without laminectomy or radiotherapy immediately after a tumor biopsy from the left mandible. The combined therapies were very effective and his neurologic symptoms improved immediately. The epidural involved masses disappeared in imaging studies after the first course of chemotherapy including methylprednisolone (20 mg/kg per day for 3 consecutive days and gradually tapered off over 2 weeks), vincristine (1.5 mg/m2 per day), cyclophosphamide (2 g/m2 per day for 2 days) and pirarubicin (40 mg/m2 per day). After completing seven courses of chemotherapy, the patient is now fully ambulant. Considering the severe late effects of laminectomy and radiotherapy, chemotherapy should be considered as a first choice of treatment for spinal cord compression caused by malignant lymphoma.

Our study is the first to demonstrate the ability to generate iPS cells from a mouse model of Pompe disease. Initially, mouse tail tip fibroblasts were harvested from male, 8-week-old (GAA) knockout mice, and three reprogramming factors (Oct3/4, Sox2 and Klf4) were transfected into the isolated donor cells using a retroviral vector. These iPS cells also showed decreased levels of GAA enzymatic activity and strong positive staining with periodic acid-Schiff (indicating the accumulation of glycogen) and acid phosphatase (lysosomal activation marker). Pompe-iPS cells were differentiated into skeletal muscle cells in Matrigel®-coated plates. Spindle-shaped skeletal muscle cells were successfully generated from Pompe-iPS cells and showed spontaneous contraction and positive staining with the myosin heavy chain antibody. Electron microscopic analysis of the skeletal muscle cells showed typical morphological features, including Z-bands, I-bands, A-bands and H-bands, which were visible in wild-type and Pompe cells. Furthermore, Pompe skeletal muscle cells accumulated massive glycogen in lysosomes. This study indicates that the iPS and skeletal muscle cells generated in this study could also be a useful disease model for studies investigating the pathogenesis and treatment of skeletal muscle in Pompe disease.